id	author	title	date	pages	extension	mime	words	sentences	flesch	summary	cache	txt
cord-261455-uejtwgar	Roschewski, Mark	Inhibition of Bruton tyrosine kinase in patients with severe COVID-19	2020-06-05		.txt	text/plain	7677	369	40	Acalabrutinib, a selective BTK inhibitor, was administered off-label to 19 patients hospitalized with severe COVID-19 (11 on supplemental oxygen; 8 on mechanical ventilation), 18 of whom had increasing oxygen requirements at baseline. This prospective off-label clinical study includes 19 hospitalized patients with severe COVID-19 who received off-label acalabrutinib between March 20, 2020 (date of treatment of the first patient) through April 10, 2020 with formal data collection completed on April 23, 2020 (Table S1 ). Our laboratory studies of ex vivo blood samples from patients hospitalized with COVID-19 revealed significantly elevated BTK phosphorylation in peripheral blood monocytes compared with healthy volunteers, demonstrating that the target of acalabrutinib is activated in these innate immune cells. BTK activation occurs in macrophages when TLRs bind single-stranded RNA, as may occur in SARS-CoV-2 infection, leading to NF-κB-dependent expression of multiple inflammatory cytokines and chemokines, including IL-6 which we observed was induced in COVID-19 monocytes and decreased in plasma following acalabrutinib treatment (Fig. 1) .	./cache/cord-261455-uejtwgar.txt	./txt/cord-261455-uejtwgar.txt